Adrenergic receptor genotype influences heart failure severity and β-blocker response in children with dilated cardiomyopathy

Sushma Reddy, Alan Fung, Cedric Manlhiot, Elif Seda Selamet Tierney, Wendy K. Chung, Elizabeth Blume, Beth D. Kaufman, Elizabeth Goldmuntz, Steven Colan, Seema Mital

Research output: Contribution to journalArticle

Abstract

Background:Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and β-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).Methods:Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: α2cdel322-325, β1Arg389, and β2Arg16. Data were analyzed by genotype and β-blocker use. Mean age at enrollment was 8.5 y.Results:One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While β-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving β-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving β-blockers (interaction P < 0.05).Conclusion:Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of β-blocker therapy before progression to decompensated HF.

Original languageEnglish (US)
Pages (from-to)363-369
Number of pages7
JournalPediatric research
Volume77
Issue number2
DOIs
StatePublished - Feb 11 2015
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Reddy, S., Fung, A., Manlhiot, C., Selamet Tierney, E. S., Chung, W. K., Blume, E., Kaufman, B. D., Goldmuntz, E., Colan, S., & Mital, S. (2015). Adrenergic receptor genotype influences heart failure severity and β-blocker response in children with dilated cardiomyopathy. Pediatric research, 77(2), 363-369. https://doi.org/10.1038/pr.2014.183